? R-??S-???????

1
????????
? R-??S-??????? ??????????????
??????????? ??????????? ????????????
????????? ??,???,??,??? ?????????????
DDG gt 3 kcal/mol
2
?????? Reagent control
Bothner-By 1951
1972, 1973
0-78?
R Et, t-Bu
??????

1962 ??????? ???
1965 ?????? ???????
95ee
3
LiAlH4??????????????????????????
???
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???I
??????????????????
?????????
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?????????????????????????????
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E. J. Corey? ?????1987
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E. J. Corey ?????????
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???????? ?????????
????????,0.05 ?????????(BH3)????? ??1????
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???????????????????????????????
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E. J. Corey 1989
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???????????(????????)
-
Li
BH3
CBS
???????????? ???????????
?? resolution
?? transformation
??????? Intramolecular chirality transfer
??????? Intermolecular chirality transfer
???? chiral multiplication
???? chiral amplification
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???????????????????? ??????????????????????
(S)-BINAP??????
?????
????????
(S)-BINAP????????
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???????????
?????????????(??)
?????????????(?)
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??????Dynamic Kinetic Resolution Ru-BINAP/H2
?????
??????
slow
fast
Ru-(S)-BINAP
slow
Ru-(R)-BINAP
fast
fast
fast
slow
slow
??????
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?????????
0.97
95
4
0.03
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?????????????????????
D. J. Cram 1952
67
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Cram model (Cram rule)
acyclic
dipolar
cyclic
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Cram model ??????????
Felkin-Ahn model
Cram-type
dipolar-type
?????
???
Felkin-Ahn model ?????????
???
cyclic-type
anti-Cram-type
??????????????
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Cram-type?anti-Cram-type ????????
anti-Cram-type
1 2.8
Cram-type
22 1
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?? aldol ??
aldol ????homo-aldol??
K 10 16-20 0.0001
???????
aldol ????cross-aldol??
???????
LDA
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??????????????
base ??
anti
(Z)-enolate (Z)-?????
syn
?? ??? syn/anti
??
??
?????????
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??????????????
base ??
anti
(Z)-enolate (Z)-?????
syn
????????? ?????
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??
???
?????
?????
???
??
?????
?????
??????????
???????
??????
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???????????????????????????????
(E)-????? 86 14
???(anti)
(Z)-????? 100 0
??(syn)
?
(E)-?????
(Z)-?????
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???????????????????????????????

72de
enolate
???????????? ??????
enolate
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??????????????????????????????
?? (MIT)
D. A. Evans (Harvard)
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Evans ??????????????????
Mp 71?72 ? aD 14.8
Mp 120?121 ? aD 163.7
? ???????????? ? ??????????? ? ?????????? ?
???????????????? ? ?????????????????? ee????
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Evans ???????????????????
Et3N
????????
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Evans ????????????????
????????????? ?????????(SN2)
??????? ?????
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D. Enders?????????????????????
LDA
????????
????????
SAMP
?????(SN2)
????
RAMP
LAH
NaI/MeI
R-O-NO
LAH
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D. Enders?????????
LDA, Et2O -78 ?
R3X, Et2O -110 ?
excess, Et2O, 60 ? 100
????
16N HCl, n-pentane
OH?
Air
????????
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D. Enders????????????
??????
?????
?????
???N?N????
94? 99 ee
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D. Enders?????????????????
1. LDA, Et2O, 0? 2. RBr, -110? 3. Exceaa CH3I,
50? 4. 3N HCl, pentane 70
SAMP 87
gt95ee Daddy longlegs Deffence substance
1. BuLi 2. C6H5CH2Cl

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